Imagine being a researcher and having access to funding to perform a dream experiment. For CCLCM student Darren Liu (’24), winning the 2022 VeloSano Trainee Dream Experiment Fellowship is going to allow him to do just that.
Made possible through support from VeloSano Bike to Cure and offered through the Case Comprehensive Cancer Center, the Dream Experiment Fellowship provides $10,000 of funding for highly innovative experiments that are high-risk and high-reward. The funding gives researchers the chance to undertake a single or limited set of experiments to address a critical issue in cancer research.
Darren’s project focuses on using spatial proteomic profiling to investigate tissue-specific tumorigenesis in context of PTEN hamartoma tumor syndrome.
“My project seeks to identify molecular signatures and their associated biological pathways that drive organ-specific carcinogenesis in PTEN hamartoma tumor syndrome,” says Darren, whose research mentor is Charis Eng, MD, PhD, Professor of Molecular Medicine, and Chair and founding Director of the Genomic Medicine Institute at Cleveland Clinic.
PTEN is one of the most frequently mutated tumor suppressor gene in sporadic (not inherited) cancers. Germline mutations cause PTEN hamartoma tumor syndrome (PHTS), which significantly increases the lifetime risk of cancers in certain organ systems. However, the molecular mechanism why certain tissue types with PTEN mutations are more prone to developing cancer than other tissue types with PTEN mutations is unclear.
“Using tissue obtained from autopsy from a patient with PHTS with multiple cancers, we plan to examine protein expression patterns from both non-cancer and cancer tissue at single cell/subcellular resolution in spatial relationship to one another to provide insight on how specific tissue microenvironments influence cancer initiation.
“If we’re successful, these observations may facilitate more accurate high-risk organ surveillance in patients with PHTS and help us to develop more precise molecular therapies for the more common sporadic cancers,” says Darren.
The true prevalence of PHTS in the general population is unknown because it is difficult to recognize and, thus, believed to be under-diagnosed. Germline mutations of PTEN not only contribute to an increased cancer risk, but they have also been identified in up to 20% of children with autism spectrum disorder and macrocephaly (large head).
Darren, who hopes to combine his interests in gastroenterology and cancer genetics in his future clinical practice, anticipates completing his dream experiment within 12 months.